Introduction to Peripheral Neuropathy

Cancer, Chemotherapy, and Peripheral Neuropathy

Peripheral neuropathy is associated with several types of cancers and is thought to affect as many as 5% of cancer patients. Cancer-related neuropathies are usually caused by the spread of cancer to the nervous system or compression of a tumor on a nerve. However, most cases of peripheral neuropathy experienced by cancer patients are caused by neurotoxic side effects of the drugs used for chemotherapy. Since chemotherapy is designed to destroy cancer cells, it also damages or destroys other healthy cells in the body, including peripheral nerve cells.

Toxic chemotherapeutic agents interfere with the metabolic needs of the nerve cells which in many cases, leads to degeneration or injury to the axon, myelin sheath, or cell body of sensory, motor and/or autonomic neurons. Typically symptoms follow the 'stocking-glove' pattern where they first appear at the most distal point (the toes and feet) which is the most vulnerable to injury, and progress proximally towards the center of the body, a pattern called "dying back".

Chemotherapy-related neuropathy is generally length dependent, meaning the symptoms begin in the toes or feet and is usually a sensory or sensorimotor neuropathy. It can be very painful and debilitating and can severely impact quality of life. The earliest symptoms, such as paresthesia and numbness, may occur between the first and third cycle of chemotherapy. Motor weakness is not as common but if it develops, usually occurs later since motor axons are myelinated which offers some protection from initial injury, whereas most sensory neurons are unmyelinated. Some neuropathies are dose related and worsen with cumulative doses. Some appear after the first dose while others may appear following several doses of medication and may even develop after chemotherapy has been stopped, a process known as "coasting". Sensory symptoms are described as negative symptoms (such as numbness), or positive symptoms (such as pain and paresthesia). Sensory disturbances are common to almost all chemotherapy-related neuropathies and have a significant impact on quality of life.

The appearance of peripheral neuropathy associated with chemotherapy generally follows a pattern which includes:

• Symptoms initially appear distally in toes and feet and progress proximally
• When the symptoms have progressed up the legs to approximately the level of the knees or above, symptoms may begin to be felt in the fingertips
• Symptoms may form a "tear-drop" pattern around the abdomen
• Patient may experience myalgia (muscle pain) or muscle cramps that are exacerbated by activity
• Autonomic symptoms such as dry mouth or orthostatic hypotension may develop
• Pain may develop with some neuropathies and may be severe

Neurotoxic chemotherapeutic agents include:

• Plant alkaloids (e.g., vinorelbine, vincristine)

  • causes paresthesia (abnormal sensations; tingling) in the hands and feet of up to 60% of patients
  • may cause gait disturbances and muscle weakness.
  • considered to be the least neurotoxic of the chemotherapeutic agents

• Taxanes (e.g., paclitaxel, docetaxel)

  • causes degeneration and demyelination of the axon
  • affects autonomic cardiovascular function (e.g., blood pressure)
  • symptoms may include burning, dysesthesia (unpleasant sensation), or paresthesia
  • sensory loss from paclitaxel develops in up to 70% of patients
  • neuropathy from paclitaxel appears in some patients after the first dose and tends to increase with prolonged treatment
  • sensory loss from docetaxel occurs in up to 50% of patients.
  • docetaxel is not as neurotoxic as paclitaxel and patients may experience spontaneous recovery when treatment is discontinued
  • in general, patients may experience improvement in symptoms from neuropathy over a long period of time
  • when combined with platinum-based drugs, a high percentage of patients develop sensorimotor neuropathy.

• Platinum-based drugs (e.g., cisplatin, oxaliplatin, or carboplatin)

  • highly associated with small fiber sensory neuropathy (numbness, paresthesia)
  • large fiber nerves may be affected
  • up to 60% of patients receiving platinum-based medications suffer from peripheral neuropathy
  • oxaliplatin is associated with dysesthesia caused by contact with anything cold and muscle contractions
  • symptoms may persist or progress for several months beyond the treatment period
  • the neuropathic side effects of these drugs can be a factor in limiting the dosage given for treatment

• Interferons - these drugs boost the immune system and are used to treat certain types of cancers. Interferons have been reported to cause peripheral neuropathy in some patients.

• Thalidomide - this drug causes neuropathy which results in sensory more than motor neuropathy. Its effects on the nervous system are long lasting and while some patients recover slowly, others do not recover at all.

Other neuropathic symptoms associated with cancer chemotherapy include:

• Burning
• Painful numbness
• Allodynia (pain due to a stimulus which does not usually cause pain, e.g., light touch)
• Acroparesthesia (tingling/numbness in legs); this is often the earliest and most persistent symptom.
• Muscle weakness
• Hypoflexia (diminished muscle reflexes)

• Autonomic symptoms such as:

  • postural hypotension - drop of blood pressure with postural or positional change; it is one of the most common manifestations of autonomic involvement
  • cardiac irregularities
  • bladder/bowel dysfunction

Recovering from chemotherapy-related peripheral neuropathy can be very slow and sometimes symptoms may be even more intense during the recovery period. Regenerating nerves can cause cramping and paresthesia that are severe and significantly interfere with daily activities. Patients who had previous neuropathy are at highest risk for developing chemotherapy-related peripheral neuropathy. As cancer treatment evolves with the use of higher doses of drugs and combinations of increasingly potent drugs, the number of cases of chemotherapy-related peripheral neuropathy is expected to increase.

To read more about chemotherapy-related peripheral neuropathy, please click on the following link: http://www.medifocus.com/abstracts.php?gid=NR021&ID=18367040